Nutritional status and immune function are closely related [1][2][3]. Food deprivation leads to impaired immune responses and an increase in the incidence of infectious disease, although the mechanism by which this occurs has yet to be elucidated. Adipose tissue preserves energy homeostasis through the storage of triglycerides. However, it has been found recently that a number of cytokine-like molecules, such as leptin [4], tumour necrosis factor-a (TNF-a) [5] and plasminogen activator inhibitor-1 (PAI-1) [6] are secreted from adipocytes, suggesting that adipose tissue may also play a role in the regulation of the immune and haematopoietic systems.Leptin is secreted specifically by adipocytes [4], and serum leptin levels are proportional to body mass index. However, the placenta [7] and stomach [8] provide additional sources of leptin. Leptin decreases food intake, increases energy expenditure and reduces body weight via leptin receptors within the ventromedial hypothalamus [9], where leptin functions to inhibit the production of neuropeptide Y which stimulates food intake [10]. The murine leptin and leptin-receptor mutants ob/ob and db/db, respectively, serve as animal models of obesity, and develop marked obesity and diabetes due to deficiencies in leptin signalling [11]. In contrast, leptin transgenic mice with elevated plasma leptin concentrations lack brown or white adipose tissue, show reduced food intake, and are markedly lean in comparison with non-transgenic littermates [12].The leptin receptor is expressed in peripheral tissues such as the kidney, lung and adrenal gland [13,14], and several in vitro studies have demonstrated that leptin acts directly on the leptin receptor [15,16]. There are at least five splice variants of the leptin receptor Ob-Ra-Ob-Re, and one of these five variants, Ob-Rb, possesses a long intracellular domain demonstrating homology with gp130, a subunit of the IL-6 family of cytokine receptors [17]. On the other hand, Ob-Ra, one of the shortest forms of the leptin receptor, lacks the STAT3 activation domain and is not considered essential for signal transduction [18].Recent studies have revealed that Ob-Rb is expressed in fetal liver haematopoietic precursor cells, bone marrow and peripheral T cells [14,19]. In adult human bone marrow, both CD34 positive and negative cells express leptin receptor. These findings suggest the possibility that leptin not only regulates body weight, but also modulates the immune system. Indeed, leptin increases the proliferation of haematopoietic stem cell populations at the multilineage progenitor level [18], enhances alloproliferative mixed-lymphocyte reactions, and reverses cellular immune function in fasted mice [20]. In addition, leptin might act as a growth factor for both myeloid leukaemic cells [21] and lung cancer cells [22]. In addition, human white blood cell counts are correlated with body mass index and serum leptin levels [23]. Moreover, diminished cell-mediated immunity and decreased lymphocyte counts have been reported in ob/ob and db...
